{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:53:08Z","timestamp":1777909988615,"version":"3.51.4"},"reference-count":36,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>To determine the pharmacokinetics of a proprietary liposomal sirolimus (LS) formulation in ocular tissues and plasma following a single subconjunctival (SCJ) injection in Dutch belted rabbits (DBR). Analytical methods for detection of LS in plasma, aqueous humor (AH), vitreous humor (VH), retina, combined retina\/choroid\/retinal pigment epithelium, sclera, and iris\/ciliary body were developed to examine samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Thirty male DBR were subconjunctivally injected in both eyes with 0.1\u2009mL of LS of 1,000\u2009\u03bcg\/mL. At selected times post-injection, ocular tissues and whole blood samples were obtained. Sirolimus concentrations were measured using liquid chromatography\/tandem mass spectrometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>No LS was detected in serum or AH at any time. All other examined ocular tissues had quantifiable amounts of LS at all times. LS levels were highest in sclera and lowest in VH, suggesting LS followed the supraciliary and suprachoroidal spaces to reach the posterior segment. Vitreous peak of sirolimus levels occurred at 2\u2009h, and the sclera adjacent to the injection peaked at both 2 and 96\u2009h. LS levels in remaining ocular tissues peaked at 6\u2009h and decreased with time, persisting at presumed therapeutic levels on day 22.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>LS can quickly diffuse into posterior intraocular tissues after SCJ injection without reaching quantifiable levels in AH or serum in DBR. Peak levels occurred in posterior intraocular tissues at 6\u2009h and persisted in all tissues after 3 weeks. SCJ LS in DBR is safe, has a stable pharmacokinetic profile, and should be considered for further study in human trials for autoimmune ophthalmopathies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2022.0030","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T13:49:41Z","timestamp":1657806581000},"page":"424-432","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetics of Sirolimus in a Novel Liposome Delivery System in Selected Ocular Tissues and Plasma Following a Single Subconjunctival Injection in Dutch Belted Rabbits"],"prefix":"10.1177","volume":"38","author":[{"given":"Dennis","family":"Brooks","sequence":"first","affiliation":[{"name":"University of Florida, Gainesville, Florida, USA."},{"name":"Brookseyes LLC, Alachua Florida, Florida, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2186-9314","authenticated-orcid":false,"given":"Monica Anayatzin","family":"Linares-Alba","sequence":"additional","affiliation":[{"name":"Laboratorio Santgar F\u00f3rmulas Magistrales de M\u00e9xico SA de CV, Mexico City, Mexico."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7939-5222","authenticated-orcid":false,"given":"Rodrigo","family":"Garcia-Santisteban","sequence":"additional","affiliation":[{"name":"Hospital Veterinario Oftalvet, Mexico City, Mexico."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enli","family":"Xie","sequence":"additional","affiliation":[{"name":"Absorptions Systems California, LLC (ASC), San Diego, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenwood","family":"Gum","sequence":"additional","affiliation":[{"name":"Absorptions Systems California, LLC (ASC), San Diego, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda L.","family":"Manza","sequence":"additional","affiliation":[{"name":"Absorptions Systems California, LLC (ASC), San Diego, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucila","family":"Servitje-Azcarraga","sequence":"additional","affiliation":[{"name":"School of Medicine, Universidad Panamericana, Mexico City, Mexico."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego G.","family":"Santisteban","sequence":"additional","affiliation":[{"name":"Laboratorio Santgar F\u00f3rmulas Magistrales de M\u00e9xico SA de CV, Mexico City, Mexico."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo Adolfo","family":"Garc\u00eda-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Laboratorio Santgar F\u00f3rmulas Magistrales de M\u00e9xico SA de CV, Mexico City, Mexico."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"crossref","unstructured":"Weiner A. 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